Synthesis, characterization, DNA binding/cleavage, cytotoxic, apoptotic, and antibacterial activities of V(IV), Mo(VI), and Ru(II) complexes containing a bioactive ONS‐donor chelating agent

Abstract

New V(IV), Mo(VI), and Ru(II) complexes containing the ligand 2,4‐dihydroxyacetophenone‐S‐methyl dithiocarbazate (H2dhasm); [VO(dhasm)(bpy)] (1) (bpy = 2,2′‐bipyridine), [VO(dhasm)(phen)] (2) (phen = 1,10‐phenanthroline), [MoO2(dhasm)(imz)] (3) (imz = imidazole), [MoO2(dhasm)(DMSO)] (4) (DMSO = dimethylsulfoxide), and [Ru(CO)(PPh3)2(dhasm)] (5) have been synthesized. The ligand and its complexes were structurally characterized by elemental analyses, IR, 1H NMR, EPR, ultraviolet (UV)–visible spectroscopies, magnetic susceptibility, and cyclic voltammetry measurements. Single crystal X‐ray crystallography was used to establish the structure detail of (3) and (4) complexes confirming that the ligand coordinate to the metal ion in a bi‐negative tridentate fashion (dhasm2−, ONS‐donor) in a distorted octahedral geometry. The interaction with calf thymus DNA (CT DNA) of all compounds was studied by UV–visible and fluorescence spectroscopies. Both studies confirmed that these compounds bind to CT DNA through intercalation mode. The DNA cleavage activity of the complexes was also studied on plasmid DNA using gel agarose electrophoresis, and the results revealed that only complexes (2) and (5) have superior cleavage activity in the presence of H2O2. The cytotoxic activity (in vitro) of the complexes on three human cancer cell lines; human liver hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF7), and epitheliod carcinoma (Hela); and a normal human lung fibroblast (WI‐38) was studied using MTT assay. The complexes exhibited a strong cytotoxicity effect compared with their parent ligand. The ruthenium(II) complex (5) showed the most potent growth inhibition of cancer cells. Also, the mechanism of the apoptotic death in HepG2 cells was studied by observing an increased gene expression of caspase‐3, BAX, P53 and decreased Bcl2 gene expression. The complexes were also screened for their antibacterial activity against gram‐positive and gram‐negative bacteria and showed significant activity against both microorganisms.

Water-Soluble Dioxidovanadium(V) Complexes of Aroylhydrazones: DNA/BSA Interactions, Hydrophobicity, and Cell-Selective Anticancer Potential

“…Complex 1 , with a selectivity index (SI) of 5.24, is the most promising complex for HT-29 cells for effective antiproliferative activity. Nonetheless, under similar conditions all 1 – 5 show cytotoxic potential comparable to that of existing chemotherapeutic drugs such as cisplatin. , Moreover, the reported complexes showed promising cytotoxicity, in comparison to earlier reports of the related oxidovanadium complexes [KVO 2 (L 3 )] n and [KVO 2 (L 4 )­(H 2 O)] n (H 2 L 3 = (2,3-dihydroxy-benzylidene)-2-hydroxybenzohydrazide and H 2 L 4 = (2,3-dihydroxybenzylidene)­benzohydrazide] against the MCF-7 cell line (>200 μM), [VO­(sal-L-tryp)­(MeATSC)]·1.5C 2 H 5 OH (sal-L-tryp = N -salicylidene- l -tryptophanate, MeATSC = 9-anthraldehyde- N (4)-methylthiosemicarbazone) and [VO­(sal-L-tryp)­(N-ethhymethohcarbthio)]·H 2 O against the HT-29 cell line (>80 μM), and [V IV O­(1-(2-hydroxyphenyl)­diazenyl)­naphthane-2-ol)­(phen/bipy)] against the HeLa cell line (>44 μM) …”

“…Nonetheless, under similar conditions all 1−5 show cytotoxic potential comparable to that of existing chemotherapeutic drugs such as cisplatin. 116,117 Moreover, the reported complexes showed promising cytotoxicity, in comparison to earlier reports of the related oxidovanadium complexes [KVO 2 (L 3 )] n and [KVO 2 (L 4 )(H 2 O)] n (H 2 L 3 = (2,3-dihydroxy-benzylidene)-2-hydroxybenzohydrazide and H 2 L 4 = (2,3-dihydroxybenzylidene)benzohydrazide] against the MCF-7 cell line (>200 μM), 118 against the HeLa cell line (>44 μM). 35 As per DNA and BSA binding studies, 2 was expected to show greater toxicity, but 1 with an IC 50 value of 5.42 ± 0.15 μM was as the most cytotoxic compound, whereas 4, with an IC 50 value of 72.19 ± 0.12 μM, was the least cytotoxic among all.…”

Mo(VI) Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations

“…The IC 50 values indicate that these complexes may act differently on different cell lines ascertaining them to be cell specific. Overall, the IC 50 values for Mo complexes (Table ) were found to be comparable or better than that of cisplatin, a commonly used chemotherapeutic drug. − …”

New mixed ligand copper(II) hydrazone‐based complexes: Synthesis, characterization, crystal structure, DNA/RNA/BSA binding, in vitro anticancer, apoptotic activity, and cell cycle analysis

“…The test compounds were dissolved in a minimum amount of DMSO to assist solubility (should not exceed 0.1%-0.5% v/v to avoid its toxic effect on living cells. [94][95][96] The cell viability parentage against concentration through incubation periods The cytotoxic activity of each compound was determined using IC 50 (50% inhibitory concentration) (Figure 11 and Table S3, ESI †) and therapeutic index (TI = IC50 of normal cell to IC 50 of neoplastic cell ratio) (Figure 12 and Table S4, ESI †). It has been found that the cell proliferation showed a concentration and timedependent response to the test compounds.…”

“…The test compounds were dissolved in a minimum amount of DMSO to assist solubility (should not exceed 0.1%–0.5% v/v to avoid its toxic effect on living cells. [ 94–96 ] The cell viability parentage against concentration through incubation periods 24 and 48 h are presented in Figure 10 (representative examples) and Figure S8, ESI.…”